Reaction Steps
A dry 1 L round-bottomed flask equipped with a magnetic stirrer was charged (+)-pseudoephedrine (13.92 g, 84.26 mmol, 1.0 equiv), triethylamine (13.39 mL, 96.06 mmol, 1.14 mmol), and tetrahydrofuran (340 mL). The solution was cooled to 0° C. and phenylacetyl chloride (14.33 g, 92.69 mmol, 1.1 equiv) was added via cannula over a 20 minute interval as a solution in tetrahydrofuran (90 mL). After 30 minutes, the reaction was quenched with saturated sodium bicarbonate. The amide was extracted from brine (1 L) with ethyl acetate (400 mL, 130 mL, 130 mL), and the organic extracts were dried over sodium sulfate. After removal of the solvent under reduced pressure, a solid was obtained. The solid was recrystallized from 2:1:1 ether/dichloromethane/hexanes (500 mL), affording the phenylacetamide (17.90 g, 75% yield) as a white powder: mp 145°-146° C.; 1H NMR (300 MHz, C6D6) δ6.9-7.5 (m, 10H), 4.55 (br, 1H), 4.48 (t, 1H, J=7.1 Hz), 4.11 (m, 1H), 3.95 (m, 1H), 3.83 (m, 1H), 3.78 (s, 2H), 3.31 (d, 2H, J=1.3 Hz), 2.76 (s, 3H), 2.12 (s, 3H), 0.95 (d, 3H, J=7.0 Hz), 0.42 (d, 3H, J=6.7 Hz); 13C NMR (75.5 MHz, CDCl3) δ173.1, 172.2, 142.2, 141.4, 135.5, 134.5, 128.7, 128.64, 128.58, 128.3, 128.1, 127.5, 126.73, 126.68, 126.6, 126.3, 76.2, 75.3, 58.6, 41.8, 41.4, 33.3, 27.0, 15.0, 14.3; FTIR (neat film) cm-1 3393 (br, m), 1618 (s), 1494 (m), 1453 (m), 1402 (m); HRMS (FAB) Calcd for C18H22NO2 (MH+): 284. 1652. Found: 284.1646.
